AHFS Class:
Generic Name(s):
- Benzphetamine Hydrochloride
Chemical Name:
- (+)- N -Benzyl- N ,α-dimethylphenethylamine hydrochloride
Molecular Formula:
Notification FDA drug safety communication (5/11/2023): To address continuing concerns of misuse, abuse, addiction, and overdose of prescription stimulants, FDA is requiring updates to the Boxed Warning and other information to ensure the prescribing information is consistent across the entire class of these drugs.r500 The current prescribing information in some prescription stimulants does not provide up to date warnings about the harms of misuse and abuse, particularly when these drugs are shared with individuals for whom they are not prescribed.r500 An FDA review found that most individuals who misuse prescription stimulants obtain their drugs from family members or peers, and that such sharing of prescription stimulants was a major contributor to nonmedical use and addiction.r500 Updates will include information that patients should never share their prescription stimulants with anyone, and the Boxed Warning information will describe the risks of misuse, abuse, addiction, and overdose consistently across all medicines in the class.r500 The Boxed Warning will also advise healthcare professionals to monitor patients closely for signs and symptoms of misuse, abuse, and addiction.r500 |
Benzphetamine hydrochloride, a sympathomimetic amine, is a substituted amphetamine that is used as an anorexigenic agent.r1,r473
Obesity
Benzphetamine is used as an adjunct to caloric restriction in the short-term treatment (a few weeks) of exogenous obesity in patients with an initial body mass index (BMI) ≥30 kg/m2 who have not responded to lifestyle interventions (diet and/or exercise) alone.r1 Benzphetamine is indicated for use as monotherapy only.r1 The limited usefulness of agents of this class should be weighed against their possible risks.r1
The amphetamines were the first class of drugs approved for short-term pharmacologic treatment of obesity; however, most amphetamines have been withdrawn from the US market due to adverse events and the potential for addiction.r473 In short-term placebo-controlled trials of amphetamine derivatives, patients who received active drugs demonstrated weight loss of approximately 0.5 pounds (0.23 kg) per week more than placebo.r473 However, the amount of weight loss in clinical trials has varied, and the observed increase in weight loss may be attributed to non drug-related factors.r1,r473
Guidelines from the American Gastroenterological Association (AGA) recommend the addition of pharmacologic agents in adults with obesity or overweight with weight-related complications who have had an inadequate response to lifestyle interventions.r472 Selection of an appropriate drug or intervention should be based on the clinical profile and needs of the patient, including comorbidities, patient preferences, costs, and access.r472 Given the chronic nature of weight management, long-term pharmacologic therapy is usually necessary in patients with obesity who have an inadequate response to lifestyle interventions alone.r472 Benzphetamine is indicated only for the short-term treatment of obesity.r1
General 
Pretreatment Screening
- Consider a baseline cardiac evaluation to detect pre-existing valvular heart disease or pulmonary hypertension prior to initiation of benzphetamine treatment.r1
Patient Monitoring
- An echocardiogram (ECG) during and after treatment could be useful for detecting any valvular disorders which may occur.r1
Administration
Benzphetamine hydrochloride is administered orally.r1
Dosage
Dosage of benzphetamine hydrochloride should be individualized according to patient response.r1 When the drug is used as an adjunct in the short-term treatment of exogenous obesity, the manufacturer suggests an initial adult dosage of 25-50 mg once daily, preferably given in midmorning or midafternoon according to the patient's dietary habits; it may be desirable to avoid late afternoon administration in some patients.r1 The dose or frequency of administration may be subsequently increased based on patient response and tolerability.r1 The suggested dosage ranges from 25-50 mg 1-3 times daily.r1 However, the least amount feasible should be prescribed or dispensed at one time to avoid the possibility of overdosage.r1
Special Populations
Hepatic Impairment
Manufacturer makes no special dosage recommendations.r1
Renal Impairment
Manufacturer makes no special dosage recommendations.r1
Geriatric Patients
Manufacturer makes no special dosage recommendations.r1
Contraindications
- Patients with advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to sympathomimetic amines, and glaucoma.r1
- Patients who are in an agitated state or who have a history of drug abuse.r1 (r1)
- Concomitant use or use within 14 days following monoamine oxidase inhibitors.r1
- Concomitant use with other CNS stimulants.r1
- Women who are or may become pregnant.r1
Warnings/Precautions
Pulmonary Hypertension
Benzphetamine should not be used in combination with other anorectic agents, including prescribed drugs, over-the-counter (OTC) preparations, and herbal products.r1 In a case-control epidemiological study, the use of anorectic agents was associated with an increased risk of developing pulmonary hypertension, a rare, but often fatal disorder.r1 The use of anorectic agents for longer than 3 months was associated with a 23-fold increase in the risk of developing pulmonary hypertension.r1 Increased risk of pulmonary hypertension with repeated courses of therapy cannot be excluded.r1 Benzphetamine was not specifically studied in this case-control study.r1
If exertional dyspnea or unexplained symptoms of angina pectoris, syncope, or lower extremity edema occurs, discontinue benzphetamine immediately and evaluate patient for possible pulmonary hypertension.r1 The potential risk of serious adverse effects such as pulmonary hypertension should be assessed carefully against the potential benefit of weight loss in patients in whom benzphetamine is being considered.r1 A baseline cardiac evaluation should be considered to detect pre-existing pulmonary hypertension prior to initiation of benzphetamine treatment.r1
Valvular Heart Disease
Valvular heart disease associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine has been reported.r1 Possible contributing factors include use for extended periods of time, a higher than recommended dose, and/or use in combination with other anorectic drugs.r1 However, no cases of valvulopathy have been reported when benzphetamine was used alone.r1
The potential risk of possible serious adverse effects such as valvular heart disease should be assessed carefully against the potential benefit of weight loss in patients in whom benzphetamine is being considered.r1 A baseline cardiac evaluation should be considered to detect pre-existing valvular heart disease prior to initiation of benzphetamine treatment.r1 Benzphetamine is not recommended in patients with known heart murmur or valvular heart disease.r1 An ECG during and after treatment could be useful for detecting any valvular disorders which may occur.r1 To limit unwarranted exposure and risks, treatment with benzphetamine should be continued only if the patient has satisfactory weight loss within the first 4 weeks of treatment (i.e., weight loss of at least 4 pounds, or as determined by the physician and patient).r1
Abuse Potential, Dependence, and Tolerance
Benzphetamine is subject to control as a schedule III (C-III) drug.r1
Benzphetamine is chemically and pharmacologically related to the amphetamines.r1 Amphetamines and related stimulant drugs have been extensively abused, and the possibility of abuse of benzphetamine should be considered when evaluating whether to include the drug as part of a weight reduction program.r1 Abuse of amphetamines and related drugs may be associated with intense psychological dependence and severe social dysfunction.r1 There are reports of patients who have increased the dosage to many times that recommended.r1 Abrupt cessation following administration of prolonged high dosages results in extreme fatigue and mental depression; changes are also noted on the sleep electroencephalogram (EEG).r1 Manifestations of chronic intoxication with anorectic drugs include severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes.r1 The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia.r1
When tolerance to the anorectic effect of benzphetamine develops, the recommended dosage should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued.r1
Comorbid Conditions
Benzphetamine is not recommended in severely hypertensive patients or patients with symptomatic cardiovascular disease including arrhythmias.r1 Caution is advised when prescribing amphetamines for patients with even mild hypertension.r1
Recent Use of Anorectic Agents
Benzphetamine is not recommended for patients who used any anorectic agents within the prior year.r1
Insulin Requirements
Insulin requirements in patients with diabetes mellitus may be altered with use of anorexigenic drugs and concomitant dietary restrictions.r1
Psychological Effects
Psychological disturbances have been reported in patients who receive an anorectic agent together with a restrictive dietary regime.r1
Specific Populations
Pregnancy
Benzphetamine may cause fetal toxicity when administered to pregnant women.r1 Amphetamines have been shown to be teratogenic and embryotoxic in animals at dosages higher than the recommended human dosage. Benzphetamine is contraindicated in women who are or may become pregnant.r1 If benzphetamine is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus.r1
Lactation
Amphetamines are excreted in human milk.r1 Mothers taking amphetamines should be advised to refrain from nursing
Pediatric Use
Safety and effectiveness of benzphetamine in patients <17 years of age have not been established.r1
Geriatric Use
Clinical studies of benzphetamine did not include sufficient numbers of subjects ≥65 years of age to establish safety and efficacy in this population.r1 In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.r1
Common Adverse Effects
Adverse effects of benzphetamine have included palpitation, tachycardia, elevated blood pressure, isolated reports of cardiomyopathy and ischemic cardiac events associated with chronic use, overstimulation, restlessness, dizziness, insomnia, tremor, sweating, headache, psychotic episodes, depression following withdrawal of the drug, dryness of the mouth, unpleasant taste, nausea, diarrhea, urticaria and other allergic skin reactions, and changes in libido.r1
Antihypertensive Agents
Amphetamines may decrease the hypotensive effect of antihypertensives.r1
Antidepressants, Tricyclics
Amphetamines may enhance the effects of tricyclic antidepressants.r1
CNS Stimulants
Benzphetamine should not be used concomitantly with other CNS stimulants.r1
Monoamine Oxidase Inhibitors
Hypertensive crises have resulted when sympathomimetic amines have been used concomitantly or within 14 days following use of monoamine oxidase inhibitors.r1
Other Anorectic Agents
Efficacy of benzphetamine in combination with other anorectic agents has not been studied and the combined use may have the potential for serious cardiac problems.r1
Benzphetamine should not be used in combination with other anorectic agents, including prescribed drugs, over-the-counter (OTC) preparations, and herbal products.r1
Description
Benzphetamine hydrochloride is an amphetamine congener that is used as an anorexigenic agent. The pharmacologic activity of the drug is similar to the amphetamines and includes CNS stimulation and elevation of blood pressure.r1
Substituted amphetamines, such as benzphetamine, have stronger inhibitory effects on serotonin reuptake transporters.r473 As with other amphetamine derivatives, no primary effect on appetite has been demonstrated with benzphetamine and it is probable that its anorexigenic effect is secondary to CNS stimulation.r1
Advice to Patients
- Amphetamines may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving a motor vehicle; the patient should therefore be cautioned accordingly.r1
- Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.r1
- Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.r1
- Inform patients of other important precautionary information.r1 (See Cautions.)
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Benzphetamine hydrochloride is subject to control under the Federal Controlled Substances Act of 1970 as a schedule III (C-III) drug.
Benzphetamine Hydrochloride
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|
Oral | Tablets, film-coated | 50 mg* | Benzphetamine Hydrochloride Tablets (C-III) | |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions May 30, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
r1. KVK-Tech. Benzphetamine hydrochloride tablets prescribing information. Research Newtown, PA; 2022 Jun.
r472. Grunvald E, Shah R, Hernaez R, et al. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology. 2022 Nov;163(5):1198-1225. Epub 2022 Oct 20. [PubMed 36273831]
r473. Coulter AA, Rebello CJ, Greenway FL. Centrally Acting Agents for Obesity: Past, Present, and Future. Drugs. 2018 Jul;78(11):1113-1132.
r500. FDA drug safety communication. FDA updating warnings to improve safe use of prescription stimulants used to treat ADHD and other conditions; issued May 11 2023. From FDA website. [Web]